Selective membrane permeability changes to small ions from an integral part of physiologically important cell functions such as the generation of electrical impulses in nerve and muscle cells, the release of neurotransmitters and hormones, sensory transduction, epithelial transport, and the activation of immune responses. The molecular mechanisms by which the ion channels underlying these essential cell activities generate regulated and selective changes in cell membrane permeability are not well understood. The goal of the proposed research is to characterize the influences of particular structural features and membrane interactions on the ion channels involved in actions potential generation (Na and K channels) and neuromuscular transmission (AChR channels). The permeation of ions through Na and K channels is regulated by the transmembrane voltage through interaction of the membrane potential with charged groups or dipoles of the channels. Experiments in this proposal will use single channel and multichannel electophysiological techniques to investigate how specific chemical modifications of charged groups influence channel activation and permeability properties at the molecular level. Specific chemical modifications will also be used to investigate the role of charged groups and disulfide bonds in determining the conductance properties of single AChR channels. Intramembranous proteins like ion channels are known to be affected by their membrane environment. Experiments in this proposal will examine how the properties of AChR channels are influenced by other membrane components. The experiments will study the electrical properties of purified AChR channels reconstituted into membrane vesicles of defined composition.